This is an application for continued support for years 31-35 of a postdoctoral training program in genetics based in the Department of Molecular and Human Genetics (DMHG). The DMHG is a bridging department with major clinical activities and strong programs in basic science research, but the emphasis of this postdoctoral program is on medical and human genetics and on molecular approaches. There are 73training faculty, 45 with primary and 28 with secondary appointments in the DMHG. Dr. Beaudet has served as Program Director for many years except for a brief hiatus and is currently Chair of the DMHG. Major research areas in the Program include cloning human disease genes, mutation analysis, molecular diagnostics, molecular cytogenetics, biochemical studies of inborn errors of metabolism, genomic imprinting, molecular basis of dysmorphology syndromes, somatic gene therapy, cloning mouse genes, developmental biology in the mouse, gene targeting in the mouse, genetic control of morphogenesis and development in Drosophila, development of new technologies for mouse genetics, control of cell cycle, function of chromosomal telomeres, bacterial recombination, genomic sequencing, and genetics of neurologic aldisorders. Trainees include MD or MD/PhD candidates seeking combined clinical and research training or seeking strictly research training, trainees of various degrees seeking combined laboratory diagnostic and research training, and PhD trainees seeking primarily research training in human or nonhuman genetics. The MD trainees generally have completed primary training in pediatrics or medicine, and PhD trainees most often come directly from completion of graduate school. A major focus of the program is to attract highly qualified MD and MD/PhD trainees who seek clinical training but are also seeking an intensive and substantial research experience. Major strengths of the training environment include a large clinical genetics component;large and sophisticated diagnostic laboratories in cytogenetics, biochemical genetics, and molecular genetics;60,000 sq. ft. of DMHG space in the basic science building;strong institutional commitment;a genetic graduate student program with relevant course work;an American Board of Medical Genetics (ABMG) certified training program;a high national ranking for research funding;a large program in human genomic sequencing;an NIH funded Mental Retardation Research Center;and overall depth in molecular genetics.